The microvascular resistance reserve: one size fits all, but mostly one

This commentary refers to ‘Microvascular resistance reserve: diagnostic and prognostic performance in the ILIAS registry’, by C. K. M. Boerhout et al., https://doi.org/10.1093/eurheartj/ehad378 and the discussion piece ‘Microvascular resistance reserve, does one size fit all?’, by T. P. J. Jansen et al., https://doi.org/10.1093/eurheartj/ehad691. We express our gratitude to the authors for their interest in our study and their insightful interpretation of the results. We greatly appreciate their remarks and we are pleased to provide our responses. First, the authors note that our study predominantly includes a patient group in which the presence of coronary microvascular dysfunction (CMD) is often not assessed and frequently overlooked. However, it should be emphasized that it is within this specific patient group, that the theoretical advantages of the microvascular resistance reserve (MRR) are observed. In the population with non-obstructive epicardial coronary artery disease, defined by either quantitative analysis (diameter reduction <50%) or by fractional flow reserve (above 0.80), the MRR correlates extremely well with coronary flow reserve. Therefore, it is unlikely that MRR offers additional benefits beyond what the CFR provides. Our study confirms this and even suggests that in patients with grey-zone haemodynamic epicardial disease (FFR 0.75–0.85), the advantages of MRR over CFR appear minimal.1 Although these findings should be validated, it is even more important that future research should explore the benefits of MRR compared to CFR especially in patients with concurrent epicardial disease. It is increasingly recognized that a comprehensive diagnostic approach interrogating all vascular domains of the coronary circulation may lead to improved clinical outcomes in patients with anginal symptoms.2 Second, the authors raise a pertinent question concerning the underlying cause of the potential prognostic superiority of MRR in patients with haemodynamically significant epicardial disease (FFR <0.75). Notably, individuals with an abnormal MRR (<3.0) and functionally significant epicardial disease exhibit similar events to those within the entire population, dominated by repeated revascularization. This could be due to the fact that CMD may correlate with a more aggressive progression of atherosclerotic burden, thereby increasing the risk of epicardial complications.3 Furthermore, CMD seems to play a role in persistent angina post-revascularization, leading to repeated (and possibly ineffective) revascularization decisions by treating clinicians.4 These insights should serve as inspiration for future research endeavours. Third, the authors inquire about the distinction between functional and structural CMD. As previously mentioned, in cases involving vessels with haemodynamically non-significant or grey-zone epicardial disease, there is a strong correlation between CFR and MRR. Consequently, using the MRR instead of CFR should theoretically not result in altered conclusions. However, this aspect could be subject of interest for future analyses. We concur with the authors’ assertion that the MRR holds the potential as an index for evaluating the vasodilator capacity of the coronary circulation, while its advantages over CFR are predominantly in patients with concomitant functionally significant epicardial disease. Furthermore, the MRR could be derived regardless of the method employed for intracoronary pressure and flow measurements (i.e. Doppler-derived, bolus or continuous thermodilution-derived). However, in this respect, it is essential to underscore that the MRR does not obviate the potential for overestimation of flow metrics by bolus thermodilution.5 Future research endeavours should aim to corroborate and expand upon the insights of our study, shedding more light on the role of the MRR in the diagnostic evaluation of anginal symptoms.